PROJECT SUMMARY Optical coherence tomography (OCT) is uniquely able to achieve micron depth resolution while imaging a large 3-dimensional (3D) volume. This enables 3D imaging and precise measurements in the anterior segment of the eye, including the cornea, conjunctiva, sclera, anterior chamber, iris, and crystalline lens. Anterior segment OCT is already widely used in ophthalmology. But a number of high-impact applications were held back by limited speed, range, penetration, and disease-specific algorithms. Therefore the specific aims are to: (1) Develop ultrahigh performance OCT for anterior eye. A novel vertical-cavity surface-emitting laser (VCSEL) will be used to develop an OCT prototype with ultrahigh-speed, wide-field, long-range, and high- penetration. The high speed and penetration will allow blood vessel imaging (angiography) in iris tumors. The wide field and long range will enable accurate whole anterior-segment biometry from the apex of the cornea to the posterior surface of the crystalline lens, which will take intraocular lens (IOL) formulas and custom scleral contact lens design to a new level of accuracy. (2) Develop OCT angiography (OCTA) of iris tumors. Distinguishing between benign and malignant tumors, including deadly melanomas, is crucial for planning treatments that minimize damage to sensitive eye tissues and reduce the risk of metastasis. Increased vascularity marks malignant transformation in tumors. The proposed ultrahigh performance OCT prototype will enable OCTA in tumors with sufficient penetration to characterize both tumor vasculature and volume. Novel software algorithms will be used to suppress motion, projection, and shadow artifacts, segment tissue boundaries, and calculate quantitative vascular density and tortuosity measurements. The technology could be useful in the evaluation of tumor angiogenesis elsewhere. (3) Improve OCT-based IOL power formula. Previously we developed an OCT-based IOL formula that improved cataract surgery refractive outcome in post-myopic LASIK eyes. We now propose to further improve the OCT-based IOL formula so that it could improve refractive outcome in all cataract surgeries, and be used to select toric as well non-toric IOL. The long-range OCT can accurately measure the crystalline lens equatorial position to improve the prediction of IOL position, which is a crucial variable that currently limits the accuracy of IOL formulas. High-speed OCT together with ray-tracing will enable more accurate net corneal power and astigmatism measurements, especially in post-radial keratotomy and post-hyperopic LASIK eyes. (4) Improve scleral lens fitting with wide-field OCT. Scleral contact lens vaults over the cornea and offers an important nonsurgical option to restore comfort and vision to patients with irregular corneal shape or ocular surface inflammation. The primary limitation of scleral lens is the difficult trial-and-error fitting process. We will use wide-field OCT corneoscleral topography to improve the selection of the initial trial lens and design advanced radially asymmetric scleral lenses that are highly customized to the subject ocular surface.